Download Biol115_2014_Lecture 9_The Central Dogma

Biol115
The Thread of Life"
Lecture 9"
Gene expression and the
Central Dogma"
“... once (sequential) information has passed into protein it
cannot get out again.”"
~Francis Crick, 1958
!
Principles of Biology & other references"
•  Chapter ‘ Gene Expression’ (What is the central dogma)"
•  Chapter ‘ Non-coding RNA’ (Overview only)"
•  http://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology"
•  http://discovermagazine.com/2009/oct/03-sea-change-challengingbiologys-central-dogma"
•  Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227,
561-563."
Biol115_2014_Lecture 9"
2"
Objectives"
•  Explain the flow of biological information between the key
molecules involved in transcription and translation."
•  Examine criticisms and evidence ‘against’ the Central Dogma."
•  Key terms: central dogma, transcription, translation, reverse
transcription, RNA viruses, prions, RNA editing, non-coding
RNA"
Biol115_2014_Lecture 9"
3"
Development of the Central Dogma"
Crick proposed the Central Dogma to indicate the direction of
information flow: from nucleic acid to proteins."
All possible directions of information flow"
By 1958, some arrows were removed"
Biol115_2014_Lecture 9"
4"
The Central Dogma of Biology"
http://www.mun.ca/biology/scarr/Central_Dogma.gif"
•  The Central Dogma specifies that biological information
stored in DNA is used to synthesise proteins via an RNA
intermediate."
•  The information flow is largely unidirectional, from DNA to
protein."
•  The information in DNA is also replicated before cell division."
Biol115_2014_Lecture 9"
5"
Genetic information is used to synthesise
proteins"
•  Genetic information
refers to the linear
sequence of nucleotides
in DNA."
•  The linear sequence of
nucleotides in DNA
specifies a linear
sequence of amino acids "
Linear sequence of amino acids = polypeptide or protein!
Biol115_2014_Lecture 9"
6"
RNA as viral genetic material "
•  The broadest variety of RNA genomes is found in viruses that
infect animals"
•  Retroviruses use reverse transcriptase to copy their RNA
genome into DNA"
•  HIV (human immunodeficiency virus) is the retrovirus that
causes AIDS (acquired immunodeficiency syndrome)!
Biol115_2014_Lecture 9"
7"
RNA as viral genetic material"
•  The viral DNA that is integrated into the host genome is called a
provirus!
•  Unlike a prophage, a provirus remains a permanent resident of
the host cell"
•  The host’s RNA polymerase transcribes the proviral DNA into
RNA molecules"
•  The RNA molecules function both as mRNA for synthesis of
viral proteins and as genomes for new virus particles released
from the cell"
Biol115_2014_Lecture 9"
8"
Insert Fig. 19-8 P391"
Biol115_2014_Lecture 9"
9"
Insert Fig. 19-7 P390"
Biol115_2014_Lecture 9"
10"
Prions: the simplest infectious agents"
•  Prions are slow-acting, virtually indestructible infectious
proteins that cause brain diseases in mammals"
•  Prions propagate by converting normal proteins into the prion
version"
•  Scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob
disease in humans are all caused by prions"
Biol115_2014_Lecture 9"
11"
Prions and Mad Cow disease"
Section of "
a brain from"
a patient suffering from
Creutzfeldt-Jakob disease
(CJD) or spongiform
encephalopathy (SE)"
http://hygienicsystems.com/images/CJD.jpg"
Biol115_2014_Lecture 9"
12"
What are prions?"
•  related to normal
proteins of unknown "
function"
"
Two versions of these
proteins:"
•  normal = PrP"
•  abnormal = PrP*"
"
PrP"
PrP*"
" models of normal PrP protein and abnormal,
3-D
infectious PrP* "
http://www.mad-cow.org/00/image_archive.html"
Biol115_2014_Lecture 9"
13"
Why did prions challenge the
Central Dogma?"
•  prion = infectious protein that appeared to replicate itself"
•  Central Dogma = only DNA can produce new protein"
Resolution of conflict:"
•  New prions are formed by structural change of host
prion-like proteins, not by synthesis of new protein."
Biol115_2014_Lecture 9"
14"
Lesson learned from prion infections: the Central
Dogma is still valid"
“The central dogma of molecular
biology deals with the detailed
residue-by-residue transfer of
sequential information. It states
that such information cannot be
transferred from protein to either
protein or nucleic acid.” (F.H.C.
Crick, 1970)!
Biol115_2014_Lecture 9"
15"
RNA editing"
5 November 2010 | Nature | doi:10.1038/news.2010.586 "
19 May 2011 | Nature | doi:10.1038/news.2011.304 "
"
RNA editing is the site-specific modification of an RNA sequence
from that of its template by mechanisms other than splicing."
"
Results in changes to the sequences of mRNA such that the message
no longer reflects the genetic code in DNA."
"
THR SER SER HIS"
ACG UCG AGA CAU(mRNA)"
Original Sequence"
"
ACG UCG UGA CAU (mRNA)"
THR SER *
HIS"
Edited Sequence"
"
"
Biol115_2014_Lecture 9"
16"
Editing of Glutamate receptor mRNA
in human neurons"
Unlike RNA splicing, RNA
editing changes the code in
mRNA (without changing
the code in DNA)"
Editing produces glutamate
receptor proteins with
varying receptor functions"
Nishikura Nature Reviews Molecular Cell Biology
7, 919–931 (December 2006) | doi:10.1038/
nrm2061"
Biol115_2014_Lecture 9"
17"
http://www.neuroscience.cam.ac.uk/uploadedFiles/greger_phplHaWZR.jpg"
Biol115_2014_Lecture 9"
18"
Non-coding RNAs & heterochromatin
formation"
Non-coding
RNA can
silence genes
– i.e. inhibit
gene
expression"
Non-coding RNA (e.g. siRNA) can convert
euchromatin into non-expressed
heterochromatin."
The non-coding RNA Xist (red) coats one of the
two X chromosomes in females, compacting it into
heterochromatin and inactivating it."
Biol115_2014_Lecture 9"
19"
Challenge to the Central Dogma"
•  While RNA editing and non-coding RNA can alter the expression
of genes, these phenomena do not invalidate the central dogma."
•  “…once ‘information’ has passed into protein it cannot get out again.”!
Biol115_2014_Lecture 9"
20"
You should now be able to:"
1.  Describe information flow in biological systems using the
Central Dogma of molecular biology "
2.  Explain how RNA viruses, prions, RNA editing and non-coding
RNA may be used as examples to contradict the Central
Dogma (although they do not)."
3.  Describe how RNA editing provides a powerful mechanism to
produce biological variation that is not of genetic origin."
4.  Explain why mechanisms such as RNA editing and non-coding
RNA-mediated gene silencing produce phenotypic variation,
but that those variations are not genetic (heritable)."
Biol115_2014_Lecture 9"
21"